MAFLD is associated with increased all-cause mortality in low cardiovascular-risk individuals but not in intermediate to high-risk individuals

Background and aimsMetabolic-associated fatty liver disease (MAFLD) is increasingly recognized as a systematic disease rather than just a liver disease alone, which raises concerns about its long-term impact on different populations. This study aimed to clarify the effects of MAFLD on long-term outcomes among different cardiovascular risk-stratified populations.Methods and resultsEligible individuals in the Third National Health and Nutrition Examination Surveys (NHANES Ⅲ, 1988–1994) were enrolled. Participants were classified into low, intermediate, or high cardiovascular-risk populations according to the Framingham general equations. Kaplan-Meier survival analysis and Cox regression models were used to investigate the association between MAFLD and long-term outcomes in different cardiovascular-risk populations.A total of 8897 adults were enrolled in the final analysis. The median ages in the non-MAFLD and MAFLD groups were 44 and 49 years old, respectively. During a median follow-up of 22.8 years, a total of 2991 deaths were recorded, including 1694 deaths (30.3%) in non-MAFLD and 1297 deaths (39.2%) in MAFLD (P < 0.001). In the low cardiovascular-risk population, MAFLD individuals had increased all-cause mortality than non-MAFLD individuals (HR = 1.206, 95% CI:1.0338-1.400, P = 0.014). However, similar results were not observed in intermediate or high-cardiovascular-risk individuals. Further analysis of cause-specific mortality suggested that MAFLD was associated with higher cancer-related mortality in the low-risk population (HR = 1.313, 95% CI:1.000-1.725, P = 0.049).ConclusionsMAFLD was associated with increased all-cause mortality among individuals with low cardiovascular risk, rather than those with an intermediate or high cardiovascular risk.     

A quantitative assessment of the number of disease foci in papillary thyroid cancer

AimMultifocality is a frequent feature of papillary thyroid carcinoma (PTC). Its prognostic value is controversial although national guidelines recommend treatment intensification if present. However, multifocality is not a binary but discrete variable. This study aimed to examine the association between increasing number of foci and risk of recurrence following treatment.Methods577 patients with PTC were identified with median follow-up of 61 months. Number of foci were taken from pathology reports. Log-rank test was used to assess significance. Multivariate analysis was performed and Hazard Ratios were calculated.ResultsOf 577 patients, 206(35%) had multifocal disease and 36(6%) recurred. 133(23%), 89(15%) and 61(11%) had 3+, 4+ or 5+ foci respectively. The 5-year RFS stratified by number of foci was 95%v93% for 2+foci (p = 0.616), 95%v96% for 3+foci (p = 0.198) and 89%v96% for 4+foci (p = 0.022). The presence of 4 foci was associated with an over 2-fold risk of recurrence (HR 2.296, 95% CI 1.106–4.765, p = 0.026) although this was not independent of TNM staging. Of the 206 multifocal patients, 31(5%) had 4+foci as their sole risk factor for treatment intensification.ConclusionAlthough multifocality per se does not confer worse outcome in PTC, finding 4+foci is associated with worse outcome and could therefore be appropriate as a cut-off for treatment intensification. In our cohort, 5% of patients had 4+foci as a sole indication for treatment intensification, suggesting that such a cut off could impact clinical management.     

Mean platelet volume modifies the contribution of homocysteine to cardiovascular disease: A real-world study

Background and aimsThe effect of reductions in homocysteine (Hcy) on cardiovascular disease (CVD) was suggested to be modified by platelet activation, but the interaction between Hcy and platelet activation on CVD events is not well studied. Here, we aimed to examine the interaction between Hcy and platelet activation on CVD in a large, real-world population.Methods and resultsA total of 27,234 patients with hypertension (mean 63 years, 48% male) who were registered in Taicang city and free of CVD were prospectively followed up for new CVD events from 2017 to 2020. Hcy and platelet indices including mean platelet volume (MPV) were assayed at baseline. A total of 1063 CVD events were recorded during follow-up. Hcy at baseline was significantly associated with a higher risk of CVD (HR = 1.85, P < 0.001 for log-transformed Hcy). MPV showed a significant interaction effect with Hcy on CVD (HR = 1.20, P = 0.030 for the interaction term). The association between Hcy and CVD was significantly stronger in participants with a large (vs. small) MPV (HR = 2.71 vs. 1.32, P = 0.029 for log-transformed Hcy). For participants with both elevated Hcy and a large MPV, the attributable proportion of CVD events due to their interaction was 0.26 (95% CI: 0.06–0.45).ConclusionsThe association between Hcy and CVD was significantly stronger in patients with hypertension with a larger MPV. MPV may modify the contribution of Hcy to CVD events through synergistic interactions with Hcy. These findings suggest that MPV could be monitored and controlled in the prevention of CVD.     

The management of non-diagnostic soft tissue tumour biopsies using a multi-disciplinary team approach: A 10-year retrospective review at a specialist sarcoma unit

Non-Diagnostic (ND) biopsies are occasionally encountered during the investigation of soft tissue sarcoma. We performed a retrospective review of all ND soft tissue biopsies discussed at our regional Multi-Disciplinary Team (MDT) meeting between 2004 & 2014 with the aim of establishing the incidence of ND biopsies, identifying predictive factors for repeat biopsies and evaluating the effectiveness of MDT decisions. We identified 80 ND out of 3233 biopsies. Diagnostic Yield (DY) was 97.5%, 76.0% and 77.8% for the first, second and third successive biopsy respectively. With an MDT approach utilising radiological and clinical information, the diagnostic success rate achieved was 98.5%, 82.0% and 77.8% for the first, second and third biopsies respectively. Malignant tumours (sarcoma & carcinoma) were 19 times more likely to undergo an increasing number of biopsies compared to benign lesions (p < 0.01), while repeat biopsies were less useful for suspected benign lesion. Although a repeat biopsy was only performed in 63% of cases, there were no patients originally diagnosed with a benign lesion that re-presented with the same lesion subsequently being malignant throughout the study period. Our study shows that a specialist MDT approach leads to high diagnostic rates and is a safe and effective method of preventing unnecessary, repeat biopsies where the initial biopsy is ND.     

MicroRNA-324-3p inhibits osteosarcoma progression by suppressing PGAM1-mediated aerobic glycolysis

Osteosarcoma (OS) is the most common primary malignant neoplasm of the bone. Recent studies have indicated that the inhibitory effects of microRNA (miR)-324-3p could affect the development of numerous cancers. However, its biological roles and underlying mechanisms in OS progression remain unexplored. In this study, miR-324-3p expression was markedly reduced in OS cell lines and tissues. Functionally, miR-324-3p overexpression suppressed OS progression and was involved in the Warburg effect. Mechanistically, miR-324-3p negatively regulated phosphoglycerate mutase 1 (PGAM1) expression by targeting its 3′-UTR. Moreover, high expression of PGAM1 promoted OS progression and aerobic glycolysis, which were associated with inferior overall survival in patients with OS. Notably, the tumor suppressor functions of miR-324-3p were partially recovered by PGAM1 overexpression. In summary, the miR-324-3p/PGAM1 axis plays an important role in regulating OS progression by controlling the Warburg effect. Our results provide mechanistic insights into the function of miR-324-3p in glucose metabolism and subsequently on the progression of OS. Targeting the miR-324-3p/PGAM1 axis could be a promising molecular strategy for the treatment of OS.     

Piperacillin/tazobactam and risk of acute kidney injury in adults hospitalized with infection without vancomycin: a multi-centre real-world data analysis

BackgroundThere is uncertainty about whether piperacillin/tazobactam (PT) increases the risk of acute kidney injury (AKI) in patients without concomitant use of vancomycin. This study compared the risk of hospital-acquired AKI (HA-AKI) among adults treated with PT or antipseudomonal β-lactams (meropenem, ceftazidime) without concomitant use of vancomycin.MethodsThis real-world study analysed the data from China Renal Data System and assessed the risk of HA-AKI in adults hospitalized with infection after exposure to PT, meropenem or ceftazidime in the absence of concomitant vancomycin. The primary outcome was any stage of HA-AKI according to the Kidney Disease Improving Global Outcomes guidelines. A multi-variable Cox regression model and different propensity score (PS) matching models were used.ResultsAmong the 29,441 adults [mean (standard deviation) age 62.44 (16.84) years; 17,980 females (61.1%)] included in this study, 14,721 (50%) used PT, 9081 (31%) used meropenem and 5639 (19%) used ceftazidime. During a median follow-up period of 8 days, 2601 (8.8%) develped HA-AKI. The use of PT was not associated with significantly higher risk of HA-AKI compared with meropenem [adjusted hazard ratio (aHR) 1.07, 95% confidence interval (CI) 0.97–1.19], ceftazidime (aHR 1.09, 95% CI 0.92–1.30) or both agents (aHR 1.07, 95% CI 0.97–1.17) after adjusting for confounders. Results were consistent in stratified analyses, PS matching using logistic regression or random forest methods to generate a PS, and in an analysis restricting outcomes to AKI stage 2–3.ConclusionsWithout concomitant use of vancomycin, the risk of AKI following PT therapy is comparable with that of meropenem or ceftazidime among adults hospitalized with infection.     

The impact of daptomycin therapeutic drug monitoring on clinical outcomes: a systematic review

AimDaptomycin therapeutic drug monitoring (TDM) is a potentially valuable intervention for a relatively new drug. The aim of this study was to determine whether daptomycin TDM, including dose adjustment where necessary, improves the clinical outcomes of adult patients with Gram-positive infections.MethodsA systematic review of English-language studies in MEDLINE (Ovid MEDLINE and Epub Ahead of Print, In-process, In-Data-Review & Other Non-Indexed Citations, Daily and Versions), EMBASE via OVID, Cochrane Central Register of Controlled Trials via the OVID platform, Scopus and Web of Science online databases was performed and conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. There was no discrimination on study type or time of publication.Study selectionAdults (age ≥18 years) with a Gram-positive infection requiring treatment with daptomycin who received TDM, with subsequent reporting of serum concentrations and dose adjustment where necessary, were included.ResultsIn total, 2869 studies were identified, of which nine met the inclusion criteria. No studies of daptomycin TDM including a relevant control arm have been published to date. All of the included studies were single-arm observational cohort studies. Broad heterogeneity was observed between the studies in terms of included pathogens, infection types, daptomycin TDM practices, reported clinical outcomes, and reporting of potential confounders.ConclusionsNo studies exploring the efficacy of routine daptomycin TDM on patient-centred outcomes in comparison with fixed dosing regimens have been published to date. This represents a key knowledge gap as opposed to an inherent lack of efficacy. Further well-designed, comparative studies are required to determine the role of daptomycin TDM in patients with Gram-positive infections.     

Longitudinal association between triglyceride glucose index and depression progression in middle-aged and elder adults: A national retrospective cohort study

Background and aimsPsychological symptoms are prevalent among individuals with non-communicable diseases, while the longitudinal association between triglyceride glucose (TyG) index, an indicator of metabolic health, and depression progression remains unclear yet. This study aims to investigate the association of baseline TyG index and depression progression in middle-aged and elder adults.Methods and resultsThis retrospective cohort study enrolled 8287 participants aged 45 years or above from national China Health and Retirement Longitudinal Study in visit 1 (2011–2012), which were biennially followed for depression score until visit 4 (2017–2018). Multivariate-adjusted regression models were used to evaluate the association of baseline TyG index with the individual level change rate and slope of depression score. The mean age (±SD) of participants was 58.25 ± 9.10 years, and 3806 (45.9%) were men. There was no significant difference of depression score at baseline across TyG quartile groups (P = 0.228). Participants in the highest quartile of TyG index had a 0.124 (95% CI: 0.018–0.230) higher change rate of depression score, and a 0.127 (95% CI: 0.019–0.235) higher change slope, compared to those in the lowest. The observed associations were consistent in multiple sensitivity analyses, and stable in men, the elder, and overweight people.ConclusionTyG index is positively associated with depression progression especially in men, the elder and overweight people, which provides new insights for the primary prevention of depression disorder.